Monkeys with Zika

In Ceará, researchers identify the virus in animals accustomed to the presence of humans

Victims of proximity: capuchin monkeys who live with humans were identified as having the Zika virus

Danielle Araujo / Pasteur Institute and ICB/USPVictims of proximity: capuchin monkeys who live with humans were identified as having the Zika virusDanielle Araujo / Pasteur Institute and ICB/USP

In five municipalities of the Brazilian state of Ceará, some at distances of nearly 300 kilometers apart, there are monkeys infected with the Zika virus.  Researchers from São Paulo and Ceará have identified the virus in samples of sera, oral mucosa and saliva from four marmoset and three bearded capuchin monkeys accustomed to interacting with humans in urban and rural areas of Fortaleza, Limoeiro do Norte, Quixeré, São Benedito and Guaraciaba do Norte.

The seven infected animals represent 29% of the 24 monkeys whose biological material has been analyzed in recent months – nearly 30 other samples are to be tested in the coming weeks.  “This is the first time the Zika virus has been found in New World primates,” says biologist Silvana Favoretto, a researcher at the Pasteur Institute of São Paulo and the Institute of Biomedical Sciences at the University of São Paulo (ICB-USP). Favoretto and six other researchers from São Paulo who are members of the Zika Network, a consortium of São Paulo laboratories investigating the virus, described the finding in a short article filed April 20, 2016 in the bioRxiv repository.

The Zika virus was first isolated in 1947 from the blood of a rhesus monkey (Macaca mulatta) monitored in a Uganda forest   to track circulation of the yellow fever virus. Rhesus monkeys (along with chimpanzees, gorillas and humans) belong to a group of primates called catarrhines, characterized by nostrils that are very close together and downward facing.

The virus has now been found in Ceará in the common marmoset (Callithrix jacchus) and bearded capuchin (Sapajus libidinosus), monkeys classified as platyrrhine–primates characterized by nostrils open to the side.  It is believed that platyrrhines and catarrhines shared a common ancestor between 37 million and 34 million years ago.  After that, each group evolved separately.

Identification of the Zika virus in primates of the Americas concerns matters of public health because of the risk that these animals could become what researchers call wild reservoirs of the virus.  Once infected, they could keep the virus circulating in nature and, from time to time, go back to spreading it among humans – something similar to what happens with yellow fever in some regions of Brazil.

For now, though, this is just an assumption.  The Ceará animals identified with the virus lived in close proximity to humans.  Favoretto says that marmosets frequently visit the backyards of houses in Brazil’s Northeast.  It is also common for people to keep marmosets and bearded capuchins as pets.  “These animals are docile as babies but become more unsociable and sometimes even aggressive as they grow up,” she says.  Because of this proximity, the researcher suspects that the monkeys were infected by mosquitoes that bit humans who had Zika.

“That is my main line of reasoning right now,” says primatologist Júlio César Bicca-Marques, a professor at the Pontifical Catholic University of Rio Grande do Sul (PUC-RS). “If the virus is later found in wild animals that have no contact with humans, my understanding could change,” says the researcher from Rio Grande do Sul, who years ago monitored an outbreak of wild yellow fever that affected howler monkeys in southern Brazil. Bicca-Marques says that at that time, people thought the monkeys were spreading the disease and began hunting them. Bicca-Marques and Favoretto now fear that the same type of pursuit will be directed towards the marmosets and bearded capuchins.  “Our findings show that wild animals should not be sheltered in backyards, but instead free in nature, where the chain of infections can occur without harming individuals,” Favoretto says.

Curiosity and luck
The two researchers acknowledge that for now, close to nothing is known about how the Zika virus acts in non-human primates  – especially New World primates. “For example, we don’t know if, when they get sick, their offspring are born with microcephaly or how long the virus remains in their bodies,” says Favoretto.  She and veterinarian Danielle Araujo, her colleague at the Pasteur Institute and ICB-USP, found reduced concentrations of Zika in infected marmosets and capuchins.

Identification of the virus in these animals occurred through a combination of curiosity and luck.  At the ICB-USP, Favoretto heads up the Center for Rabies Research and has spent nearly two decades studying the disease in Ceará in partnership with the state health department there.  Caused by a virus that is highly lethal to humans, rabies has a wild cycle in that northeastern state where, as identified earlier by Favoretto, the marmoset is one of the reservoirs.

In early 2016, when analyzing the distribution of cases of Zika and microcephaly in Ceará, the biologist verified that some of the cases coincided with areas from which samples of biological material from monkeys were being collected and she decided to test them for the presence of Zika.  “We found positive samples for Zika in animals that lived along the coast, in the Caatinga scrubland and in the forested mountain region where vegetation is more dense,” the researcher says. “This shows that there is widespread presence of the virus there.”

After detecting Zika in some of the samples, the genetic material of the virus was isolated and sequenced at the Clinical and Molecular Virology Laboratory of USP and analyzed by virologists Paolo Zanotto and Edison Durigon.  The findings confirmed that the Zika found in the animals is the same as that infecting humans in Brazil that could lead to the birth of babies with neurological problems and abnormally small brains – from the end of 2015 through April 23, 2016, the Ministry of Health identified 1,198 cases of microcephaly, with the Zika virus detected in 194 of the cases.

Favoretto plans to make additional expeditions to Ceará in the near future, returning to the cities where the Zika-infected animals were identified to attempt to recapture them (they were tagged with microchips).  If the monkeys continue to present copies of the virus in their bodies, it will be a sign that they can act as reservoirs.  “If this turns out to be the case, the Zika virus will have definitely come to stay since it’s difficult to eradicate diseases with wild reservoirs,” Favoretto says.  The most we’ll be able to do is keep them under control,” she says.

Rabies in terrestrial wild fauna from the Northeast region of Brazil: molecular epidemiology and detection of immune response (nº 2014/16333-1); Grant Mechanism: Regular Research Grant; Principal Investigator: Silvana Regina Favoretto (Pasteur Institute); Investment: R$296,307.41.

Scientific article
FAVORETTO, S. et al. First detection of Zika virus in neotropical primates in Brazil: a possible new reservoir. BioRxiv. April 20, 2016.